Proc. Natl. Acad. Sci. USA
Vol. 92, pp. 4442-4446, May 1995
Cell Biology
ETS1 suppresses tumorigenicity of human colon cancer cells
(transcription factor)
HIROAKI SUZUKI*t, VINCENZO ROMANO-SPICA*, TAKIS S. PAPASt, AND NARAYAN K. BHAT*§
*Laboratory of Molecular Oncology, National Cancer Institute, P.O. Box B, Frederick, MD 21702-1201; *Center for Molecular and Structural Biology, Hollings
Cancer Center, Medical University of South Carolina, Charleston, SC 29425-2213; and §Program Resources, Inc./DynCorp, Frederick Cancer Research and
Development Center, P.O. Box B, Frederick, MD 21702-1201
Communicated by Robert C. Gallo, National Cancer Institute, Bethesda, MD, January 3, 1995 (received for review June 24, 1994)
ABSTRACT
We have ectopically expressed transcription
factor ETS1 in two different highly tumorigenic human colon
cancer cell lines, DLD-1 and HCT116, that do not express
endogenous ETS1 protein and have obtained several indepen-
dent clones. The expression ofwild-type ETS1 protein in these
colon cancer cells reverses the transformed phenotype and
tumorigenicity in a dose-dependent manner. By contrast,
expression in DLD-1 cells of a variant form of ETS1, lacking
transcriptional activity, did not alter the tumorigenic prop-
erties of the cells, suggesting that the reduction in tumorige-
nicity in these clones was specific for the wild-type ETSI gene
products. Since these colon cancer cells have multiple genetic
alterations, the system described in this paper could be a good
model to study the suppression of tumorigenicity at a tran-
scriptional level, which could lead to the design and develop-
ment of novel drugs for cancer treatment.
ETS1 is a member of the ets gene family and is a cellular
counterpart of the v-ets oncogene of the avian erythroblastosis
virus E26'(1-3). The ETS1 gene is expressed at high levels in
lymphoid cells (4-9) and in astrocytes and endothelial cells
(10-12). ETS1 is a nuclear phosphoprotein (13-15) that binds
to purine-rich DNA sequences and functions as a transcription
factor (1-